Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs

Abstract

Several modifications in CA-4 were reported in literature for the development of various tubulin inhibitors. In our study, twenty-two newly synthesized heterocyclic derivatives of Combretastatin A-4 (CA-4) have been tested for their cytotoxic effect on four different types of cells with malignant behavior using CA-4 as a positive control. Compounds 5b, 15 and 16 showed the foremost potent antiproliferative activities as compared to CA-4 with IC50 starting from 6.9 to 13.7 μM. Molecular docking was performed with the crystal structure of tubulin employing a potent tubulin inhibitor CA-4 as a parent molecule. Molecular study advised that 5b, 15, 16 and 17 are promising tubulin inhibitors.